Peripheral vascular disease (PVD) is a serious medical condition that has been estimated to affect about 5% of people over the age of 50. The major clinical manifestations of PVD are those of ischemia and include pain, pallor, cramping, and loss of function of muscles, especially in the hands, feet, and legs. Severe cases of PVD can result in skin ulcerations or gangrene of an affected limb with the necessity of amputation.
The cause of PVD is a deficiency of blood supply to the peripheral circulation, that is to the arterial circulation supplying portions of the body other than the visceral organs, the brain, sensory organs such as the eye, and organs having specialized circulation such as the hypothalamus and pituitary. The peripheral circulation includes the circulation to the upper and lower extremities and, both in the extremities and in other portions of the body, to the skin, to skeletal muscle, and to bone.
PVD has been classified into two types of disorders, either functional or organic PVD. Functional peripheral vascular diseases lack an organic cause and do not involve defects in the structure of blood vessels. An example of a functional PVD is Raynaud's disease, which is a condition in which the small arteries that supply blood to the fingers and toes go into spasm when exposed to a stimulus such as cold. The term “Raynaud's disease” is used synonymously herein with “Raynaud's syndrome” and “Raynaud's phenomenon”, and is referred to hereafter simply as “Raynaud's”. The spasms of Raynaud's may also be induced by vibration, emotional upset, or cigarette smoking. Raynaud's is a common phenomenon, affecting millions of people in the United States alone. It may exist as a primary condition, that is with no associated disorder. Raynaud's may also occur as a secondary condition of other diseases such as scleroderma, lupus, or rheumatoid arthritis. There is no presently available treatment for functional PVD such as Raynaud's. Treatment for Raynaud's is aimed at removing the stimulus that causes the vasospasm. That is, affected people are instructed to avoid cold or other vasospasmogenic stimuli, to dress warmly, and to stop smoking.
Organic PVD is caused by structural changes in the blood vessels, such as inflammation, tissue damage, or the build-up of plaque. A functional PVD may exist as a component or as a contributory factor to organic PVD. An example of an organic PVD is intermittent claudication (IC). This condition, which has been estimated to affect up to 5% of men and 2.5% of women over the age of 60, is frequently due to atherosclerosis of the legs resulting in decreased blood supply. Typical symptoms of IC are cramping and intermittent pain in the legs and buttocks brought on by walking and which symptoms are relieved upon rest. If untreated, IC tends to progress and, if it becomes severe, may result in ulceration or gangrene of affected limbs, in extremely severe cases necessitating amputation. Treatment for IC includes treatment of any underlying heart disease, cessation of smoking, and the use of drugs, such as pentoxifylline and cilostazol, that prevent platelets from clotting together.
Other common causes of organic PVD include diabetes and thromboangiitis obliterans (TAO), also known as Buerger's Disease. Diabetes, due to an disorder in insulin production or secretion, is treated by administration of insulin and dietary regulation. TAO, an inflammation and thrombosis of arteries and vein in the hands and feet which is highly correlated to heavy cigarette smoking, is treated by cessation of smoking. Other therapies, such as the administration of anti-inflammatory and antithrombotic drugs, have not proven to be successful.
To date, no effective therapy exists for PVD, and no therapy exists for treating or reducing the incidence of functional PVD, whether the functional PVD exists alone or as a component or complicating factor of an organic PVD. Moreover, no therapy exists for long term administration to an individual who is susceptible to periodic episodes of symptoms due to PVD, such as to those suffering from Raynaud's.